Multiple Sclerosis

1. Multiple Sclerosis How it affects us

2. Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). It is a disease of the white matter tissue. The white matter is made up of nerve fibers which are responsible for transmitting communication signals both internally within the CNS and between the CNS and the nerves supplying rest of the body. In people affected by MS, patches of damage called plaques or lesions appear in seemingly random areas of the CNS white matter. At the site of a lesion, a nerve insulating material, called myelin, is lost. MS is hard to characterize because it is very unpredictable and variable. Depending on which areas of the CNS are affected and how badly they are damaged, the type and severity of symptoms can vary greatly. People with MS experience partial or complete loss of any function that is controlled by, or passes through the brain or spinal cord. What is Multiple Sclerosis?

3. People with MS can experience any of the following problems either fully or partially: Numbness Tingling Pins and needles Muscle weakness Muscle spasms Spasticity Cramps Pain Blindness Blurred or double vision incontinence Urinary urgency or hesitancy Constipation Slurred speech Loss of sexual function Loss of balance Nausea Disabling fatigue Depression Short term memory problems Other forms of cognitive dysfunction Inability to swallow Inability to control breathing Continued

4. What happens to the myslin?

5. This is characterized by relapses during which time new symptoms can appear and old ones worsen.. The relapses are followed by periods of remission, during which time the person fully or partially recovers from the deficits acquired during the relapse. Relapses can last for days, weeks or months and recovery can be slow and gradual. The majority of people presenting with MS are first diagnosed with relapsing/remitting. This is when the person is in their twenties or thirties, though diagnoses much earlier or later are known. Around twice as many women as men present with this variety. 4 Types of MS 1. Relapsing/Remitting(RRMS)

6. After a number of years many people who have had relapsing/remitting MS will pass into a secondary progressive phase of the disease. Characterized by a gradual worsening between relapses. In early phase, the person may still experience a few relapses but after a while these merge into a general progression. There are good and bad days but there is no real recovery. After 10 years, 50% of people with relapsing/remitting MS will have developed secondary progressive MS. 2. Secondary Progressive (SPMS)

7. 3. Progressive Relapsing MS (PRMS) • This form of MS follows a progressive course from onset, punctuated by relapses. • There is significant recovery immediately following a relapse but between relapses there is a gradual worsening of symptoms.

8. Characterized by a gradual progression of the disease from its onset with no remissions at all. There may be periods of a leveling off of disease activity and as with secondary progressive, there may be good and bad days or weeks. PPMS differs from relapsing/remitting and secondary progressive in that onset is in the late thirties or early forties. Men are as likely as women to develop it and initial disease activity is in the spinal cord instead of the brain. Often migrates into the brain, but is likely to damage brain areas than relapsing/remitting or secondary progressive. 4. Primary Progressive MS (PPMS)

9. What does MS Affect?

10. During periods of Multiple Sclerosis activity, white blood cells are drawn to regions of the with matter. These initiate and take part in what is known as the inflammatory response. The resulting inflammation is similar to what happens in your skin when you get a pimple. It seems that the inflammation also kills the maintenance glial cells, in particular it seems to kill the myelin-producing oligodendrocytes, which are lost in great numbers. Almost no oligodendrocytes persist in the middle of chronic MS lesions. As the disease progresses, axons are also destroyed though not necessarily by the inflammatory response. During the secondary progressive phase, inflammation becomes less and less common but still the axons continue to die. This degeneration of axons is known as Wallerian Degeneration.

11. After axons have been demyelinated, several things can happen: • The inflammation dies back. Neurons which have not been damaged by the relapse can resume their proper function and some recovery is usual, at least in the early stages of the relapsing/remitting form of the disease. • Demyelinated axons can exhibit remarkable abilities to function despite losing their myelin. Recent work has shown that they produce greater numbers of sodium channels. These are special chemical gates which are integral in sending nerve transmitters down the neuron. This increased number of sodium channels contributes to remission in MS. • The central nervous system is a very plastic organ and new neuronal pathways and connections can be created to get around the damaged neurons. This is anala goes to a motorist taking a minor road to avoid a traffic accident on their intended route. Although it is clear that this mechanisim contributes to remission, it is far from clear what the exact details are and much work remains to be done in this area.

12. Continued • The myelin maintenance cells in the CNS, the oligodendrocytes, can sponsor remyelination – a process when the myelin sheath around the axon is repaired. Despite the fact that evoked potential tests show that remyelinated axons don’t function quite as well as those which were never damaged in the first place, to the PwMS, this is sometimes not noticeable. Although remyelination usually only occurs at the edges of lesions, it still seems to be a contributing factor in remission. • Remyelination may not take place or only happen partially, at least for a long time, due to oligodendrocytes not being around to promote it. When this happens the nerve will continue to function in an abnormal way as described above, but the axon remains undamaged. Sometimes after a long period of time, sometimes years, an axon will spontaneously become remyelinated and regain much of the function that had been presumed to be lost for good.

13. Farther Continued • The lost myelin can be replaced with scar tissue much like when you cut your hand a scar forms to join the separated areas of skin. This scarification is how Multiple Sclerosis got its name: Multiple – many and Sclerosis – scar forming. Scar tissue can block the formation of new myelin and once axons have become scarified they do not fully regain their former function. • The underlying axon can become withered and function lo9st entirely. Needless to say a withered axon will never function at all again. Continuing our electrical wire analogy, this is rather like snipping the cable with wire cutters.

14. For more information go to: http://www.mssociety.ca/ http://medstat.med.utah.edu/kw/ms/